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IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models

Pancreatic ductal adenocarcinoma (PDAC) and cancer-associated cachexia (CAC) are multifactorial and characterized by dysregulated inflammatory networks. Whether the proinflammatory cytokine IL-20 is involved in the complex networks of PDAC and CAC remains unclear. Here, we report that elevated IL-20...

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Autores principales: Lu, Shao-Wei, Pan, Hong-Chin, Hsu, Yu-Hsiang, Chang, Kung-Chao, Wu, Li-Wha, Chen, Wei-Yu, Chang, Ming-Shi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490368/
https://www.ncbi.nlm.nih.gov/pubmed/32929072
http://dx.doi.org/10.1038/s41467-020-18244-8
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author Lu, Shao-Wei
Pan, Hong-Chin
Hsu, Yu-Hsiang
Chang, Kung-Chao
Wu, Li-Wha
Chen, Wei-Yu
Chang, Ming-Shi
author_facet Lu, Shao-Wei
Pan, Hong-Chin
Hsu, Yu-Hsiang
Chang, Kung-Chao
Wu, Li-Wha
Chen, Wei-Yu
Chang, Ming-Shi
author_sort Lu, Shao-Wei
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) and cancer-associated cachexia (CAC) are multifactorial and characterized by dysregulated inflammatory networks. Whether the proinflammatory cytokine IL-20 is involved in the complex networks of PDAC and CAC remains unclear. Here, we report that elevated IL-20 levels in tumor tissue correlate with poor overall survival in 72 patients with PDAC. In vivo, we establish a transgenic mouse model (KPC) and an orthotopic PDAC model and examine the therapeutic efficacy of an anti-IL-20 monoclonal antibody (7E). Targeting IL-20 not only prolongs survival and attenuates PD-L1 expression in both murine models but also inhibits tumor growth and mitigates M2-like polarization in the orthotopic PDAC model. Combination treatment with 7E and an anti-PD-1 antibody shows better efficacy in inhibiting tumor growth than either treatment alone in the orthotopic PDAC model. Finally, 7E mitigates cachexic symptoms in CAC models. Together, we conclude IL-20 is a critical mediator in PDAC progression.
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spelling pubmed-74903682020-10-01 IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models Lu, Shao-Wei Pan, Hong-Chin Hsu, Yu-Hsiang Chang, Kung-Chao Wu, Li-Wha Chen, Wei-Yu Chang, Ming-Shi Nat Commun Article Pancreatic ductal adenocarcinoma (PDAC) and cancer-associated cachexia (CAC) are multifactorial and characterized by dysregulated inflammatory networks. Whether the proinflammatory cytokine IL-20 is involved in the complex networks of PDAC and CAC remains unclear. Here, we report that elevated IL-20 levels in tumor tissue correlate with poor overall survival in 72 patients with PDAC. In vivo, we establish a transgenic mouse model (KPC) and an orthotopic PDAC model and examine the therapeutic efficacy of an anti-IL-20 monoclonal antibody (7E). Targeting IL-20 not only prolongs survival and attenuates PD-L1 expression in both murine models but also inhibits tumor growth and mitigates M2-like polarization in the orthotopic PDAC model. Combination treatment with 7E and an anti-PD-1 antibody shows better efficacy in inhibiting tumor growth than either treatment alone in the orthotopic PDAC model. Finally, 7E mitigates cachexic symptoms in CAC models. Together, we conclude IL-20 is a critical mediator in PDAC progression. Nature Publishing Group UK 2020-09-14 /pmc/articles/PMC7490368/ /pubmed/32929072 http://dx.doi.org/10.1038/s41467-020-18244-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Lu, Shao-Wei
Pan, Hong-Chin
Hsu, Yu-Hsiang
Chang, Kung-Chao
Wu, Li-Wha
Chen, Wei-Yu
Chang, Ming-Shi
IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models
title IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models
title_full IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models
title_fullStr IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models
title_full_unstemmed IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models
title_short IL-20 antagonist suppresses PD-L1 expression and prolongs survival in pancreatic cancer models
title_sort il-20 antagonist suppresses pd-l1 expression and prolongs survival in pancreatic cancer models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490368/
https://www.ncbi.nlm.nih.gov/pubmed/32929072
http://dx.doi.org/10.1038/s41467-020-18244-8
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